AB0041 THE PHENOTYPE OF PERIPHERAL BLOOD DENDRITIC CELLS OF PATIENTS WITH ADULT-ONSET STILL´S DISEASE COMPARED TO HEALTHY DONORS AND PATIENTS WITH PSORIATIC ARTHRITIS
Authors: S. Schnitte, T. Funk, J. Henes, S. Saur
Journal: Annals of the Rheumatic Diseases (2022)

Background Adult-onset still´s disease (AOSD) is a rare autoinflammatory disease. A triad of high fever, arthritis and skin rash is described, but multiple forms of manifestation, as the lack of detectable biomarkers, aggravate making the diagnosis (1). Psoriatic arthritis (PsA), another autoimmune disease with jointal manifestation, affects approximately 30% of all patients with psoriasis (2). Dendritic cells (DCs) are potent antigen presenting cells linking adaptive and innate immunity. In various autoimmune diseases alterations of DCs were detected (4). Objectives The etiology and effect of peripheral blood DCs on the arthritis in both diseases is not cleared yet (1,3). This project tried to examine alterations of DCs in AOSD patients compared to those with PsA and a healthy control group (HC). Methods 13 patients with AOSD were analysed and compared. Leukocytes were separated with density gradient centrifugation and sorted with flow cytometry. The contingent of DC subsets in the peripheral blood (pDCs, CD1c+DCs, CD141+DCs) was compared between AOSD patients and the other two groups (n=12). Monocytes of the peripheral blood were incubated with IL-4 and GM-CSF to differentiate to DCs. The addition of lipopolysaccharides helped gaining immature (n=11) and mature (n=9) DCs. Their phenotype was characterized by CD1a, CD206, Osteoactivin (OA), CCR7, CD14, DC sign, CCR7, CD14, CD40, HLA-DR, CD80, CD83, CD86. The expression levels of the surface proteins were again compared. Results The DC subset rates did not differ significantly between AOSD patients and both other groups. The surface markers showed a significant difference in expression of CD80 on mature DCs of AOSD patients and those with PsA. Immature DCs presented a significantly different level of OA on patients with AOSD and HCs. All other measured surface markers did not vary between the groups. Conclusion The DC subsets analysis did not show significant differences. An arthritic manifestation in AOSD might not depend on the fraction of DCs in the peripheral blood. OA inhibits T cell responses strongly as coinhibitory molecule on antigen presenting cells. The lower expression of OA on DCs of patients with AOSD might represent a lower inhibition of T cells in comparison to HCs (5). The interaction of CD80 and CD86 with CD28 is necessary to produce IL-6. The pro-inflammatory effect is limited by CD80/ CD86 itself (6). CD80, in contrast to CD86, is expressed differently in patients with AOSD and PsA. As CD80 and CD86 function as cofactors, an alteration of both might have been expected. References [1]Efthimiou P, Kontzias A, Hur P, Rodha K, Ramakrishna GS, Nakasato P. Adult-onset Still’s disease in focus: Clinical manifestations, diagnosis, treatment, and unmet needs in the era of targeted therapies. Semin Arthritis Rheum. 2021;51(4):858-74. [2]Henes JC, Ziupa E, Eisfelder M, Adamczyk A, Knaudt B, Jacobs F, et al. High prevalence of psoriatic arthritis in dermatological patients with psoriasis: a cross-sectional study. Rheumatol Int. 2014;34(2):227-34. [3]Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018;391(10136):2273-84. [4]Takenaka MC, Quintana FJ. Tolerogenic dendritic cells. Semin Immunopathol. 2017;39(2):113-20. [5]Gutknecht M, Geiger J, Joas S, Dörfel D, Salih HR, Müller MR, et al. The transcription factor MITF is a critical regulator of GPNMB expression in dendritic cells. Cell Commun Signal. 2015;13:19. [6]Lanier LL, O’Fallon S, Somoza C, Phillips JH, Linsley PS, Okumura K, et al. CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. J Immunol. 1995;154(1):97-105. Disclosure of Interests Sarah Schnitte Grant/research support from: The project was financially supported by Novartis., Tanja Funk: None declared, Jörg Henes: None declared, Sebastian Saur: None declared